Chlamydiae are Gram-negative eubacteria that replicate inside eukaryotic cells. They are wide-spread pathogens responsible for, or contributing to, many diseases including preventable blindness, pneumonia, pelvic inflammatory disease, infertility, arthritis, and cardiovascular disease in humans.
Chlamydia trachomatis is an obligate intracellular pathogen consisting of three biovars. Biovar trachoma is responsible for preventable blindness, and is also a major cause of sexually transmitted infections characterized by cervicitis, endometritis and salpingitis in women, and urethritis in men, whereas biovar lymphogranuloma venereum (LGV) causes a more invasive sexually transmitted syndrome that attacks subepithelial and lymphatic tissues. Biovar mouse is not a human pathogen; however, it is a useful organism modeling human chlamydial infection in mice.
Chlamydiae including C. trachomatis have a unique developmental cycle, which begins with attachment of an infectious elementary body (EB) to the host cell that internalizes the bacterium into a vacuole termed inclusion. In the inclusion, the EB differentiates into the non-infectious, metabolically active reticulate body (RB), which replicates by binary fission. Around the midpoint of the developmental cycle, the majority of RBs start to reorganize back to EBs which are then released to infect additional cells. Mammalian cells express a wide range of metalloproteases; many of them are inhibited by hydroxamates. The molecular mechanisms underlying the intracellular development of Chlamydiae remain largely undefined.
Infection by members of the genus Chlamydiae induces significant inflammatory responses. For example, genital lesions produced by Chlamydia trachomatis frequently elicit a vigorous influx of lymphocytes, macrophages, and plasma cells, suggesting the development of humoral and cellular immunity. Yet, clinically, the initial infection is frequently varied in symptomatology and may even be asymptomatic. Once fully established, the Chlamydia are difficult to eradicate, with frequent relapse following antibiotic therapy.
In view of the chronic and persistent nature of chlamydial infections, there is a need for reliable methods for the prevention of pathogenic infection as well as therapeutic approaches to manage the infection.